Recruiting
Phase 1

ABBV-324

Sponsor:

AbbVie

Code:

NCT06858813

Conditions

Hepatocellular Cancer

Squamous-Cell Non-Small Cell Lung Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Lenvatinib

ABBV-324

Study Details

Brief summary:

HCC is a common cancer worldwide and a leading cause of cancer-related death. Lung cancer is the most frequently diagnosed cancer in the world, and the leading cause of cancer deaths. The purpose of this study is to assess adverse events and change in disease activity when ABBV-324 is given to adult participants to treat hepatocellular cancer (HCC) or squamous-cell non-small cell lung cancer (LUSC).

ABBV-324 is an investigational drug being developed for the treatment of HCC and LUSC. Study doctors put the participants in groups called arms. Each arm receives ABBV-324 alone (monotherapy) or a comparator drug, lenvatinib followed by a safety follow-up period. Approximately 232 HCC or LUSC will be enrolled in the study in approximately 45 sites worldwide.

In the dose escalation stage participants will be treated with increasing intravenous (IV) doses of ABBV-324 until the dose reached is tolerable and expected to be efficacious. In the dose optimization stage participants will receive ABBV-324, or a comparator of oral lenvatinib. The study will run for a duration of approximately 6.5 years.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.

Conditions

Hepatocellular Cancer

Squamous-Cell Non-Small Cell Lung Cancer

Study ID

NCT06858813

Start date

Apr 14, 2025

Status verified date

Mar, 2026

Completion date

Sep, 2030

Anticipated

Primary completion date

Sep, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Hepatocellular cancer (HCC) only: Child-Pugh A classification within 7 days before Cycle 1, Day 1 dosing.
  • Laboratory values meeting the criteria outlined in the protocol.
  • QT interval corrected for heart rate (QTc) < 470 msec (using Fridericia's correction), no Grade 3 arrythmia, and no other clinically significant cardiac abnormalities.
  • Measurable disease per RECIST version 1.1.
  • Part 1 and Part 2 - participants with HCC meeting the following disease activity criteria:

  • Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology or cytology. Participants with fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma/HCC are not eligible to enroll.
  • Disease that is not amenable to surgical and/or locoregional therapies, or progressive disease after surgical and/or locoregional therapies. For participants who progressed after locoregional therapy for HCC, locoregional therapy must have been completed >= 28 days prior to baseline scan for the current study.
  • Part 1: Failure of at least 1 prior systemic treatment for HCC.
  • Part 2: Failure of at least 1 prior systemic treatment consisting of an immune checkpoint inhibitor (CPI) containing regimen for HCC, including but not limited to, atezolizumab in combination with bevacizumab or tremelimumab in combination with durvalumab. Note: Participants who have received prior lenvatinib will not be eligible for Part 2.
  • Part 1 only - participants with squamous-cell non-small cell lung cancer (LUSC) meeting the following disease activity criteria:

  • Advanced or metastatic LUSC that is not amenable to surgical resection.
  • Must have failed at least 1 prior line of therapy that included at least platinum-based chemotherapy and an immune CPI, and/or an appropriate targeted therapy (if applicable), or is not suitable for other approved therapeutic options that have demonstrated clinical benefit at the judgment of the investigator. Participants should have no more than 2 lines of prior cytotoxic chemotherapy excluding neoadjuvant and/or adjuvant. Participants who are intolerant of standard therapy are eligible.

Exclusion Criteria:

  • Unresolved clinically significant adverse events (AEs) > Grade 1 from prior anticancer therapy except for alopecia.
  • Untreated brain or meningeal metastases (i.e., participants with history of metastases are eligible provided they do not require ongoing steroid treatment for cerebral edema and have shown clinical and radiographic stability for at least 14 days after definitive therapy). Participants may continue with antiepileptic therapy if required.
  • History of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids, or any evidence of active ILD or pneumonitis on screening chest computed tomography (CT) scan.
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis.
  • History of clinically significant, intercurrent lung-specific illnesses including, but not limited to:

  • Underlying pulmonary disorder (i.e., pulmonary emboli within 3 months of the study enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion, dependence on supplemental oxygen, etc.).
  • Any autoimmune, connective tissue or inflammatory disorders with documented or suspicious pulmonary involvement at Screening.
  • Must have discontinued anticancer therapy with antineoplastic intent including chemotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within 14 days or 5 half lives of the drug (whichever is shorter) prior to the first dose of ABBV-324. Palliative radiation therapy for bone, skin or subcutaneous metastases with 10 fractions or less is permitted and not participant to a washout period.

Study Design

Enrollment

232 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part 1 Dose Escalation: ABBV-324

Participants will receive escalating doses of ABBV-324 as part of the approximately 6.5 year study duration.

experimental: Part 2 Dose Optimization Arm 1: ABBV-324 Dose 1

Participants will receive ABBV-324 dose 1 as part of the approximately 6.5 year study duration.

experimental: Part 2 Dose Optimization Arm 1: ABBV-324 Dose 2

Participants will receive ABBV-324 dose 2 as part of the approximately 6.5 year study duration.

experimental: Part 2 Dose Optimization Arm 1: ABBV-324 Dose 3

Participants will receive ABBV-324 dose 3 as part of the approximately 6.5 year study duration.

active comparator: Part 2 Comparator Arm 4: Lenvatinib

Participants will receive lenvatinib as part of the approximately 6.5 year study duration.

Interventions

Lenvatinib

Oral Capsule

ABBV-324

Intravenous (IV) Infusion

Primary outcome measure

  • Number of Participants with Adverse Events (AE)s [ Time Frame: Up to Approximately 4 Years ]
  • Number of Participants with Change in Vital Signs [ Time Frame: Up to Approximately 4 Years ]
  • Number of Participants with Change in Electrocardiogram (ECG) [ Time Frame: Up to Approximately 4 Years ]
  • Number of Participants with Change in Clinical Laboratory Tests [ Time Frame: Up to Approximately 4 Years ]
  • Objective Response Rate (ORR) [ Time Frame: Up to Approximately 4 Years ]

Central Contacts and Locations

Central contacts

ABBVIE CALL CENTER

844-663-3742abbvieclinicaltrials@abbvie.com

Locations

City of Hope National Medical Center /ID# 270526

Recruiting

Duarte, California, United States, 91010

City of Hope - Orange County Lennar Foundation Cancer Center /ID# 276120

Recruiting

Irvine, California, United States, 92618

USC Norris Comprehensive Cancer Center /ID# 271573

Recruiting

Los Angeles, California, United States, 90033

UC Irvine Medical Center /ID# 270507

Recruiting

Orange, California, United States, 92868-3201

UCLA - Santa Monica /ID# 275995

Recruiting

Santa Monica, California, United States, 90404

University of Chicago Medical Center /ID# 270517

Recruiting

Chicago, Illinois, United States, 60637

Washington University /ID# 275757

Recruiting

St Louis, Missouri, United States, 63110

Memorial Sloan Kettering Cancer Center /ID# 271228

Recruiting

New York, New York, United States, 10021-3459

Thomas Jefferson University Sidney Kimmel Cancer Center /ID# 276269

Recruiting

Philadelphia, Pennsylvania, United States, 19107

SCRI Oncology Partners /ID# 272750

Recruiting

Nashville, Tennessee, United States, 37203

More Information

Sponsor

AbbVie

Last update posted

Mar 25, 2026

Last verified

Mar, 2026

Keywords

  • Hepatocellular Cancer
  • Squamous-Cell Non-Small Cell Lung Cancer
  • LUSC
  • HCC
  • ABBV-324
  • Lenvatinib

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by AbbVie on 2026-03-25.